The roles of FXYD family members in ovarian cancer: an integrated analysis by mining TCGA and GEO databases and functional validations.

Abstract

The FXYD family of ion transport regulators have emerged as important modulators of cancer progression and metastasis. However, their expression and roles in ovarian cancer (OCa) have not been systematically investigated. The expression of FXYD genes in OCa was analyzed using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), as well as independent clinical samples. The prognostic values of FXYD genes were evaluated by Kaplan-Meier and Cox regression analysis. To explore potential mechanisms, bioinformatics approaches including Gene Ontology, KEGG pathway analysis, GSEA and drug sensitivity correlation analysis were performed. OCa cell lines overexpressing FXYD1, FXYD5 or FXYD7 were also generated and their impacts on proliferation, migration and invasion were assessed. FXYD1 and FXYD6 were significantly downregulated while FXYD3, FXYD4 and FXYD5 were upregulated in OCa tissues compared to normal tissues. FXYD1, FXYD5 and FXYD7 were independent adverse prognostic factors for OCa patients. Pathway and drug correlation analysis revealed that FXYD1, FXYD5 and FXYD7 genes regulated diverse oncogenic signaling cascades and modulated the response to various chemotherapeutic agents. Overexpression of FXYD1, FXYD5 or FXYD7 enhanced OCa cell motility and invasiveness in vitro. Our results demonstrate aberrant expression patterns, prognostic values, and oncogenic activities of FXYD genes in OCa. FXYD1, FXYD5 and FXYD7 may serve as biomarkers and therapeutic targets for this disease. Targeting FXYD-mediated signaling represents a promising therapeutic strategy against OCa.